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Genetic oncological and molecular epidemiological research on development and progression of the biliary tract cancer in Asia

亚洲胆道癌发生和进展的遗传肿瘤学和分子流行病学研究

基本信息

批准号：
12576002
负责人：
MIWA Masanao
金额：
$ 6.59万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

The COX expressions were evaluated separately in the epithelium and in the stroma of gallbladder cancer, chronic cholecystitis, xanthogranulomatous cholecystitis (XGC) and the normal gallbladder. In normal gallbladder COX-2 expression rate was significantly higher in the epithelium than in the stroma. The COX-2 expression rate in the epithelium of non-cancerous adjacent epithelium to cancerous lesion was significantly lower than those not only of cancer, but also chronic cholecystitis, XGC and normal gallbladder. In stroma, the COX-2 expression rate in cancer, chronic cholecystitis and XGC were significantly higher than that of the normal gallbladder. The rate in non-cancerous adjacent stroma to cancer is significantly lower than that of cancer and XGC. Our results suggest that COX-2 expression in the gallbladder may be regulated by various factors and not directly related to carcinogenesis.The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. To elucidate cytogenetic, we analyzed DNA copy number abnormalities of these cancers in genome-wide scale by comparative genomic hybridization. Poorly-differentiated carcinomas have more frequent chromosomal gain at 18p11 than well-differentiated carcinomas. Frequent decrease in copy number were observed at 1pter-p36 (34%) and 21q13-qter (28%). Alterations found in this study might be candidate for novel genes and prognostic factors in the intrahepatic bile duct cancer with chronic inflammation. We also found that the microsatellite instability (MSI) of intrahepatic cholangiocarcinoma in Thailand, was classified as low frequency MSI and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.

分别检测考克斯在胆囊癌、慢性胆囊炎、黄色肉芽肿性胆囊炎（XGC）及正常胆囊上皮和间质中的表达。正常胆囊组织中，考克斯-2在上皮中的表达率明显高于间质。考克斯-2在癌旁非癌上皮中的表达率明显低于癌旁上皮，也明显低于慢性胆囊炎、XGC和正常胆囊上皮。胆囊癌、慢性胆囊炎和XGC间质中考克斯-2的表达率明显高于正常胆囊组织。癌旁非癌间质中的阳性率明显低于癌和XGC。我们的研究结果表明，考克斯-2在胆囊的表达可能受到多种因素的调节，并没有直接相关的致癌作用。肝吸虫感染相关的肝内胆管癌（ICC）是一个主要的肝癌在泰国东北部。为了阐明细胞遗传学，我们通过比较基因组杂交在全基因组范围内分析了这些癌症的DNA拷贝数异常。低分化癌比高分化癌在18 p11处有更频繁的染色体获得。在1 pter-p36（34%）和21 q13-qter（28%）观察到拷贝数频繁减少。本研究中发现的变异可能是肝内胆管癌伴慢性炎症的新基因和预后因子的候选者。我们还发现，在泰国的肝内胆管癌的微卫星不稳定性（MSI），被归类为低频率MSI和DNA MMR系统，通过hMSH 2和hMLH 1基因突变，并没有发挥重要作用，在其致癌作用。